Cale). This demonstrates self-similarity in the gene segment size and spacing distribution across the V (right) and J (left) loci, with the two halves of the figure demonstrating symmetry. Log scale used.the TRA locus (electronic supplementary material, figure S2b,c). The consistency observed between the slope of decline in the V segment distance from the D or J segments and the previously Talmapimod molecular weight calculated FD-TCR supports the notion of self-similarity of the TCR loci as seen in the preceding calculations.3.2. Logarithmic scaling of the T-cell receptor gene segment periodicityIn the self-similarity analysis, the FD-TCR oscillates around a central value with regular periodicity. Further, the repetitive occurrence of gene segments on the TCR loci, suggests that they conform to a periodic distribution analogous to the cyclic behaviour LOXO-101MedChemExpress Larotrectinib exhibited by phenomenon such as wave motion, or in this case DNA helix/spiral progression. To examine the periodicity of the relative positions of gene segments on the TCR loci, they were considered as successive nucleotide sequences on the DNA helix and the angular distance betweensegments determined by using the relationship 2pxi/10.4, where xi is the initial or final nucleotide position of the ith gene segment with respect to the TCR locus origin (electronic supplementary material, figure S1). The calculated angular distance between the gene segments was further analysed by determining the distance between V and D segments in TRB. This was measured from the 50 , centromeric-end of the D segments to the 30 , telomeric-end of the V segments. These values were used to determine the coordinates of the gene segments on the DNA helix, using the trigonometric parameters, sine and cosine for the initial nucleotides (xi) relative to the locus origin. This was done for the angular distance, AD ?2pxi/10.4, and the resulting sine and cosine values for the nucleotide positions plotted against the angular distance ( f(AD) ?sin (2pxi/10.4) or cos (2pxi/10.4)) from locus origin. No clear pattern was discernable, with the sine and cosine values for each of the positions distributed randomly along the length of the TCR DNA strand (figure 3a). Given the(a)cos/sin of TRB gene segments1.5 1.0 0.5 0 ?.5 ?.0 ?.5 TRB locus 0 50 000 100 000 150 000 200 000 250 000 300 000 350 000 400 000 450rsif.royalsocietypublishing.org(b)sin/cos gene segments1.5 1.0 0.5 0 ?.5 0 ?.0 ?.J. R. Soc. Interface 13:100200 000 TRB locus 5?to 3?300400sin/cos gene segments1.5 1.0 0.5 0 ?.5 0 ?.0 ?.100200300400500600700TRA locus 5?to 3?sin/cos TRD segments1.5 0.5 ?.5 0 ?.5 100 000 200 000 300 000 400 000 500 000 600 000 700TRA locus 5?to 3?(c)1.5 1.0 0.sin/cos0 0 ?.5 ?.0 ?.5 100 000 200 000 300 000 TRA/TRB loci 400 000 500 000 600 000 700Figure 3. Logarithmic ordering of periodic TRB gene segments. (a) Angular coordinates, i.e. sine (blue diamonds) and cosine functions (red) of TRB gene segment 50 initial nucleotide’s angular distance from locus origin (50 end) plotted across the TCR loci. The x-axis depicts angular distance of gene segments from origin. (b) Sine (orange for TRB; blue for TRA) and cosine functions (green for TRB; red for TRA) of the natural logarithm of TRB gene segment 50 first nucleotide and TRA 30 last nucleotide angular distance from locus origin (50 end) plotted across the TCR loci. Angular coordinates for TRD gene segments (cosine, orange circle; sine, blue circles) within the TRA locus depicted in the third graph. (c) TRA and TRB sine and.Cale). This demonstrates self-similarity in the gene segment size and spacing distribution across the V (right) and J (left) loci, with the two halves of the figure demonstrating symmetry. Log scale used.the TRA locus (electronic supplementary material, figure S2b,c). The consistency observed between the slope of decline in the V segment distance from the D or J segments and the previously calculated FD-TCR supports the notion of self-similarity of the TCR loci as seen in the preceding calculations.3.2. Logarithmic scaling of the T-cell receptor gene segment periodicityIn the self-similarity analysis, the FD-TCR oscillates around a central value with regular periodicity. Further, the repetitive occurrence of gene segments on the TCR loci, suggests that they conform to a periodic distribution analogous to the cyclic behaviour exhibited by phenomenon such as wave motion, or in this case DNA helix/spiral progression. To examine the periodicity of the relative positions of gene segments on the TCR loci, they were considered as successive nucleotide sequences on the DNA helix and the angular distance betweensegments determined by using the relationship 2pxi/10.4, where xi is the initial or final nucleotide position of the ith gene segment with respect to the TCR locus origin (electronic supplementary material, figure S1). The calculated angular distance between the gene segments was further analysed by determining the distance between V and D segments in TRB. This was measured from the 50 , centromeric-end of the D segments to the 30 , telomeric-end of the V segments. These values were used to determine the coordinates of the gene segments on the DNA helix, using the trigonometric parameters, sine and cosine for the initial nucleotides (xi) relative to the locus origin. This was done for the angular distance, AD ?2pxi/10.4, and the resulting sine and cosine values for the nucleotide positions plotted against the angular distance ( f(AD) ?sin (2pxi/10.4) or cos (2pxi/10.4)) from locus origin. No clear pattern was discernable, with the sine and cosine values for each of the positions distributed randomly along the length of the TCR DNA strand (figure 3a). Given the(a)cos/sin of TRB gene segments1.5 1.0 0.5 0 ?.5 ?.0 ?.5 TRB locus 0 50 000 100 000 150 000 200 000 250 000 300 000 350 000 400 000 450rsif.royalsocietypublishing.org(b)sin/cos gene segments1.5 1.0 0.5 0 ?.5 0 ?.0 ?.J. R. Soc. Interface 13:100200 000 TRB locus 5?to 3?300400sin/cos gene segments1.5 1.0 0.5 0 ?.5 0 ?.0 ?.100200300400500600700TRA locus 5?to 3?sin/cos TRD segments1.5 0.5 ?.5 0 ?.5 100 000 200 000 300 000 400 000 500 000 600 000 700TRA locus 5?to 3?(c)1.5 1.0 0.sin/cos0 0 ?.5 ?.0 ?.5 100 000 200 000 300 000 TRA/TRB loci 400 000 500 000 600 000 700Figure 3. Logarithmic ordering of periodic TRB gene segments. (a) Angular coordinates, i.e. sine (blue diamonds) and cosine functions (red) of TRB gene segment 50 initial nucleotide’s angular distance from locus origin (50 end) plotted across the TCR loci. The x-axis depicts angular distance of gene segments from origin. (b) Sine (orange for TRB; blue for TRA) and cosine functions (green for TRB; red for TRA) of the natural logarithm of TRB gene segment 50 first nucleotide and TRA 30 last nucleotide angular distance from locus origin (50 end) plotted across the TCR loci. Angular coordinates for TRD gene segments (cosine, orange circle; sine, blue circles) within the TRA locus depicted in the third graph. (c) TRA and TRB sine and.
